Epidermal growth factor is a mitogen for normal and bengn breast tissue and for MCF-7 human breast cancer cells which suggests that epidermal growth factor may affect the growth of some human breast tumors in vivo. We propose to determine the role of epidermal growth factor receptor in human breast cancer by integrating clinical and biochemical data of epidermal growth factor receptor in primary and metastatic breast tumors and breast cancer cell lines. Specifically, we will determine the concentration of epidermal growth factor receptor in plasma membrane enriched fractions prepared by sucrose density gradient centrifugation of breast tumor homogenates by two independent methods: binding of 125iodine-labeled epidermal growth factors, and binding of 125iodine-labeled monoclonal antibody specific for epidermal growth factor receptor. These metods will allow us to determine the number of functional, unoccupied receptors, and the number of receptors which retain immunological reactivity. We will evaluate the clinical relevance of epidermal growth factor receptor by determining the prognostic significance of tumor receptor concentration for disease free interval and by correlating patient's response to chemotherapies and endocrine manipulations with receptor concentration. We will determine the percentage of malignant cells and stromal cells in sections of tumors which possess epidermal growth factor receptor and the relative heterogeneity of receptor level among the malignant cells using fluorescein-labeled epidermal growth factor or fluorescein-labeled monoclonal antibody specific for receptor and computer-enhanced video-intensified fluorescnece microsopy. Fundamental biochemical properties of epidermal growth factor receptor will be determined including: regulation of epidermal growth factor receptor by various hormones, by the extracellular matrix, and expression during phase of cell cycle; photoaffinityh labeling of recepotor to determine the molecular weight and subunit nature of receptor; effects of chemical modification of epidermal growth factor and its receptor on hormone binding; comparison of EFG action and receptors present on responsive (MCF-7) and nonresponsive (MDA-231) breast cancer cell lines. Integrating clinical data with biochemical data will enable us to more fully understand the role of epideraml growth factor receptor in hu man breast cancer.